Gastrointestinal helminths infect livestock causing health problems including severe diarrhoea. To explore the underlying biological mechanisms relating to development and control of diarrhoea, we compared 4 sheep that were susceptible to development of diarrhoea with 4 sheep that were diarrhoea-resistant. Transcriptomes in the tissues where the parasites were located were analyzed using RNASeq. By considering low-diarrhoea sheep as control, we identified 114 genes that were down-regulated and 552 genes that were up-regulated genes in the high-diarrhoea phenotype. Functional analysis of DEGs and PPI sub-network analysis showed that down-regulated genes in the high-diarrhoea phenotype were linked to biological processes and pathways that include suppression of 'antigen processing and presentation', 'immune response', and a list of biological functional terms related to 'suppression in immune tolerance'. On the other hand, up-regulated genes in the high-diarrhoea phenotype probably contribute to repair processes associated with tissue damage, including 'extracellular matrix organization', 'collagen fibril organization', 'tissue morphogenesis', 'circulatory system development', 'morphogenesis of an epithelium', and 'focal adhesion'. The genes with important roles in the responses to helminth infection could be targeted in breeding programs to prevent diarrhoea.