Gyrodactylids are ubiquitous ectoparasites of teleost fish, but our understanding of the host’s immune response against them is fragmentary. Here, we used RNA-seq to investigate genes involved in the primary response to infection with Gyrodactylus bullat¬arudis on the skin of guppies, Poecilia reticulata, an important model in evolutionary and behavioural research, but also one of the most common fish in the global ornamental trade. Analysis of differentially expressed genes identified orthologues of several immune-related categories, including IL-17 signaling pathway and Th17 cell differentiation, cytokine-cytokine receptor interaction, chemokine signaling pathway, NOD-like receptor signaling pathway, natural killer cell-mediated cytotoxicity, and pathways involved in antigen recognition, processing and presentation. Components of both the innate and adaptive immune responses, play a role in resistance to gyrodactylid infection. Genes involved in IL-17/Th17 response were particularly enriched among differentially expressed genes, suggesting a significant role for this pathway in fish responses to infection with ectoparasites.