Parasites impose fitness costs on their hosts. Biologists often assume that natural selection favors infection-resistant hosts. Yet, when the immune response itself is costly, theory suggests selection may instead favor loss of resistance. Intraspecific variation in immune costs are rarely surveyed in a manner that tests evolutionary patterns, and there are few examples of adaptive loss of resistance. Here, we show that when marine threespine stickleback colonized freshwater lakes they gained resistance to the freshwater-associated tapeworm, Schistocephalus solidus. Extensive peritoneal fibrosis and inflammation is a commonly observed phenotype that contributes to suppression of cestode growth and viability, but also impose a substantial cost of reduced fecundity. Combining genetic mapping and population genomics, we find that opposing selection generates immune system differences between tolerant and resistant populations, consistent with divergent optimization.

Funding provided by: Howard Hughes Medical InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000011Award Number: Funding provided by: National Institute of Allergy and Infectious DiseasesCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000060Award Number: 1R01AI123659-01A1Funding provided by: David and Lucille Packard Foundation*Crossref Funder Registry ID: Award Number: NA

Data were collected as described in Weber et al (https://www.biorxiv.org/content/10.1101/2021.08.04.455160v1). The repository includes diverse datasets involving laboratory experimental infections, flow cytometry, gene expression, population genomics, and multiple field samples of infection rates and immune traits.