Toxoplasma gondii and Neospora caninum (both Apicomplexa) are closely related cyst-forming coccidian parasites that differ significantly in their host ranges and ability to cause disease. Unlike eutherian mammals, Australian marsupials (metatherian mammals) have long been thought to be highly susceptible to toxoplasmosis and neosporosis because of their historical isolation from the parasites. In this study, the carnivorous fat-tailed dunnart (Sminthopsis crassicaudata) was used as a disease model to investigate the immune response and susceptibility to infection of an Australian marsupial to T. gondii and N. caninum. The disease outcome was more severe in N. caninuminfected dunnarts than in T. gondii-infected dunnarts, as shown by the severity of clinical and histopathological features of disease and higher tissue parasite burdens in the tissues evaluated. Transcriptome sequencing (RNA-seq) of spleens from infected dunnarts and mitogen-stimulated dunnart splenocytes was used to define the cytokine repertoires. Changes in mRNA expression during the time course of infection were measured using quantitative reverse transcription-PCR (qRT-PCR) for key Th1 (gamma interferon KEYWORDS apicomplexan parasites, cytokines, real-time PCR, transcriptomics N eospora caninum and Toxoplasma gondii (Apicomplexa: Coccidia) are tissue cystforming parasites with a worldwide distribution. Although these closely related parasites share some similar morphological and biological features, they exhibit key differences in host range and pathogenicity (1, 2). Toxoplasma gondii is regarded as one of the most successful parasites due to its capacity to infect and cause disease in essentially any mammalian or avian species (3). In humans, it is also considered a pathogen of particular significance for pregnant and immunocompromised individuals (3, 4). In contrast, N. caninum is capable of infecting many different species but is not