Abstract
Gastrointestinal nematode (GIN) infections are one of the major constraints for grazing sheep and goat production worldwide. Genetic selection for resistant animals is a promising control strategy. Whole-transcriptome analysis via RNA-sequencing (RNA-seq) provides knowledge of the mechanisms responsible for complex traits such as resistance to GIN infections. In this study, we used RNA-seq to monitor the dynamics of the response of the abomasal mucosa of Creole goat kids infected with Haemonchus contortus by comparing resistant and susceptible genotypes. A total of 8 cannulated kids, 4 susceptible and 4 resistant to GIN, were infected twice with 10 000 L3 H. contortus. During the second infection, abomasal mucosal biopsies were collected at 0, 8, 15 and 35 days post-infection (dpi) from all kids for RNA-seq analysis. The resistant animals showed early activation of biological processes related to the immune response. The top 20 canonical pathways of differentially expressed genes for different comparison showed activation of the immune response through many relevant pathways including the Th1 response. Interestingly, our results showed a simultaneous time series activation of Th2 related genes in resistant compared to susceptible kids.

Introduction
Gastrointestinal nematodes (GIN) are an important constraint on grazing ruminants worldwide. These parasites can cause mortality especially in small ruminants but their main effect is reduced productivity [1, 2]. Anthelmintic treatments are the mainstay of current treatment but are threatened by the evolution of drug resistance in parasite populations [3]. Besides, the environmental side-effect of anthelmintic residues is no longer desirable for sustainable production and the increased demand for chemical-free animal products. Therefore, there is a need for additional control strategies. The introduction of resistance to GIN traits in small ruminants breeding schemes, would be a promising sustainable method to control GIN infection [1, 4, 5].

Resistance against most of the common diseases are complex traits involving many genes, the detection of causative variations is therefore a complex task. Currently selection against GIN relies on indirect measures such as fecal egg count (FEC), packed cell volume (PCV) and blood eosinophilia [6,7,8,9]. A major disadvantage of these methods is that animals must be infected either naturally or experimentally for these measures. An alternative is the identification and the selection of genes that are responsible for resistance to GIN infection. Several studies investigated the molecular and cellular processes associated with GIN resistance in different tissues such as duodenal [10,11,12] and abomasal mucosa [13, 14] and draining lymph nodes [15,16,17,18,19] mainly in sheep. However, only a few studies have investigated the biological processes associated with GIN resistance in goats.

It has been shown that whole-transcriptome analysis via RNA-seq is a key tool to investigate the molecular mechanisms responsible for complex quantitative traits such as resistance to GIN infection [20]. A detailed understanding of the genes and biological mechanisms involved in resistance and protective immunity would provide new phenotypic and genetic markers for effective breeding schemes [21].

Previously, we investigated the transcriptome variation in response to GIN infection in goats at 42 days post-infection (dpi) [22]. The results indicated that the maintenance of the integrity of the mucosa was probably the priority for the host at this late infection stage (42 dpi). The present study aimed to identify the changes over time in the molecular pathways and immunity development in response of Creole goats to GIN infection by analyzing the transcriptome of abomasal mucosa of resistant and susceptible kids at different time points post-infection.

Materials and methods
Ethics statement
All animal care handling techniques and procedures as well as the procedures for experimental infection, tissue sampling and slaughtering were approved by the French Ethic Committee n°069 (Comité d’Ethique en Matière d’Expérimentation Animale des Antilles et de la Guyane, CEMEAAG) authorized by the French Ministry of Higher Education, Research and Innovation. The experiment was performed at the INRA Experimental Facilities PTEA (Plateforme Tropicale d’Expérimentation sur l’Animal), in Guadeloupe (French West Indies) (16° 20′ latitude North, 61° 30′ longitude West), according to the certificate number A 971-18-02 of authorization to experiment on living animals issued by the French Ministry of Agriculture.