Authors

Discussion

We study host-parasite coevolution in the European house mouse hybrid zone, where interbreeding of Mus musculus domesticus and Mus musculus musculus can lead to extreme transgressive phenotypes in hybrids. Increased resistance to various parasites, including the protozoan parasite Eimeria spp., is a transgressive phenotype that attracted interest because it might be linked with differences in fitness. However, it is questionable whether resistance is a fitness component per se, as host health might be correlated with the ability to reduce acute infection load in any direction. It is thus essential to evaluate not only resistance but the ability of hybrids to maintain health in general and during infection. 

Our study aimed to quantify the health impacts of infections with Eimeria spp. in the house mouse hybrid zone. The cross-sectional design of our established field study does not allow us to measure health impacts directly. We therefore developed an approach to infer and extrapolate health impact from laboratory infections. In a longitudinal, experimental setup, we developed a random forest model trained on immune gene expression data to predict the maximum weight lost during an infection as a proxy for the host's health. Trained on experimental laboratory infections closely replicating field infections, our model achieved high accuracy and recall in cross-evaluation. We then applied the model to a dataset of 336 mice collected in the field and inferred the health impacts of Eimeria spp—infections on wild mice. 

When infected with Eimeria, mice from the natural environment show the inflammatory phenotype indicative of weight loss in the laboratory. Hybrid mice display an inflammatory phenotype indicative of a more detrimental health impact than their pure conspecifics. Interestingly, the hybrids' more inflammatory immune status is not dependent on infection but is primarily observed in uninfected individuals. 

Hybrid mice show an increased baseline of inflammatory responses, which might lead to higher resistance and the detection of fewer parasites. The fitness consequences of this elevated immune reaction, if any, are unclear but likely rather negative than positive. The system offers the opportunity to improve our understanding of the impact of genetic diversity and genetic incompatibilities on host-parasite interaction.