External disturbances impact helminth–host interactions by affecting dynamics of infection, parasite traits, and host immune responses

1. External perturbations, such as multispecies infections or anthelmintic treatments, can alter host–parasite interactions with consequences on the dynamics of infection. While the overall profile of infection might appear fundamentally conserved at the host population level, perturbations can disproportionately affect components of parasite demography or host responses, and ultimately impact parasite fitness and long‐term persistence. 2. We took an immuno‐epidemiological approach to this reasoning and examined a rabbit–helminth system where animals were trickle‐dosed with either one or two helminth species, treated halfway through the experiment with an anthelmintic and reinfected one month later following the same initial regime. Parasite traits (body length and fecundity) and host immune responses (cytokines, transcription factors, antibodies) were quantified at fixed time points and compared before and after drug treatment, and between single and dual infections. 3. Findings indicated a resistant host phenotype to Trichostrongylus retortaeformis where abundance, body length, and fecundity were regulated by a protective immune response. In contrast, Graphidium strigosum accumulated in the host and, while it stimulated a clear immune reaction, many genes were downregulated both following reinfection and in dual infection, suggestive of a low host resistance. 4. External perturbations affected parasite fecundity, including body length and number of eggs in utero, more significantly than abundance; however, there was no consistency in the parasite‐immune relationships. 5. Disentangling the processes affecting parasite life history, and how they relate to host responses, can provide a better understanding of how external disturbances impact disease severity and transmission, and how parasites strategies adjust to secure persistence at the host and the population level.