Disease tolerance, whereby hosts decrease the per-pathogen fitness costs of infection, is an important component of an animal’s response to pathogens. Although recent work uncovered some potential mechanisms of tolerance in animals, many others remain untested. These mechanisms are likely diverse, non-mutually exclusive, and often difficult to identify if they are not part of traditionally studied immune pathways. We used RNAseq to investigate mechanisms of tolerance in the house finch-Mycoplasma gallisepticum (MG) system, for which geographic differences in the emergence and spread of MG resulted in populations with distinct tolerance. Although down-regulated inflammatory responses are associated with MG tolerance in house finches, little is known about other potential mechanisms. To investigate mechanisms of tolerance, we examined gene expression differences between non-infected and MG-infected finches from natural populations that vary in tolerance to MG. We identified hundreds of differentially expressed genes between MG-infected birds across four populations with distinct tolerance. In support of the prediction that tolerance mechanisms are diverse, we found differential expression of genes from pathways involved in antimicrobial, heat shock, and metabolic functions, among others. These results suggest that tolerance is a multi-faceted trait that integrates molecular and physiological responses to infection, both immune and non-immune related.