Transcriptomic profiling of goats' systemic immune response to Haemonchus contortus infection during primary and secondary infection

Haemonchus contortus is an economically important gastrointestinal nematode affecting small ruminants globally. Understanding immune responses during primary and secondary exposure may inform improved control strategies. This study investigated systemic immune transcriptional responses in Boer goat buffy-coat samples during early (D5) and late (D21) primary and secondary infections using RNA sequencing ( N =6; 3 animals/pool). Data were analysed using CLC Genomics Workbench, with functional enrichment assessed using STRING and immune pathways examined using KEGG. Differential gene expression analysis (p -value ≤0.05) identified 252 and 330 upregulated genes during primary infection and 373 and 269 during secondary infection at D5 and D21, respectively. Primary infection was characterised by a neutrophil-associated, pro-inflammatory signature involving CXCL8–CXCR1/2, CSF3R/CSF2R, IL-6–STAT3/5, and MYD88–MAPK signalling. Secondary infection showed an early Th2-associated signatures at D5, including STAT6 , IL4 , and IL13 upregulation. However, canonical Th2-associated genes were not upregulated at D21, GATA3 and STAT4 were downregulated in both infections, indicating time-dependent responses. Additional changes involved IL-10/IL-10R, IL-4R/IL-13RA1, SOCS, and DUSP signalling. Functional enrichment identified Th2-associated immunity, complement activation, and leukocyte migration, antigen processing and presentation, B-cell receptor, and T-cell receptor signalling. These findings indicate temporally distinct systemic responses to primary and secondary exposure, rather than sustained helper-T-cell polarization.These signatures may be reflective of altered leukocyte composition, cell-specific transcriptional regulation, or both. Overall, these findings identify candidate immune pathways and signatures associated with immune responses to H. contortus in both naïve and previously exposed hosts.and may lay a foundation for future vaccine and genetic-resistance studies.