Bovine tuberculosis (bTB), caused by Mycobacterium bovis (Mycobacterium tuberculosis complex), is a zoonotic disease that affects cattle and wildlife worldwide. These animal hosts can serve as reservoirs of infection, thus increasing the risk of human exposure and infection. In this study we quantified by RNA macroarray fluorescent hybridization and real-time RT-PCR the mRNA levels of genes differentially expressed in oropharyngeal tonsils and mandibular lymph nodes of three and seven individual non-tuberculous and tuberculous wild boars naturally exposed to M. bovis, respectively. These results demonstrated upregulation of two genes, complement component 3 (C3) and methylmalonyl-CoA mutase (MUT), in the non-tuberculous wild boars. These upregulated genes may contribute to resistance of wild boars to bTB by modifying the innate immunity, which limits the ability of the mycobacterium to infect and persist within macrophages. The C3 and MUT genes, therefore, are likely to be good candidates to study as markers of bTB resistance using functional genomics in animal model systems. Identification of genes upregulated in wild animals resistant to bTB contributes to our understanding of the mechanisms of protective immunity and resistance to mycobacterial organisms.