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Canine distemper virus (CDV) is a cause of significant disease in canids and increasingly recognized as a multi-host pathogen, particularly of non-canid families within Carnivora. CDV outbreaks in sympatric mesocarnivores are routinely diagnosed in the Forest Preserve District of Cook County, Illinois. CDV is diagnosed more commonly and the disease more severe in raccoons and striped skunks than in coyotes. Research in other species suggests host cell receptors may play a role in variable disease outcome, particularly, the signaling lymphocyte activation molecule (SLAM) located on lymphoid cells. To evaluate receptor differences, partial SLAM genes were sequenced, and predicted amino acid (AA) sequences and structural models of the proposed viral interface assessed. Of 263 aligned nucleotide base pairs, 36 differed between species with 24/36 differences between canid and non-canids. Raccoon and skunk predicted AA sequences had higher homology than coyote and raccoon/skunk sequences and 8/11 residue differences were between coyote and raccoons/skunks. Though protein structure was similar, few residue differences were associated with charge and electrostatic potential surface alterations between canids and non-canids. RNAScope ® (Advanced Cell Diagnostics, Silicon Valley, USA) ISH revealed low levels of expression that did not differ significantly between species or tissue type. Results suggest that differences in host receptors may impact species-specific disease manifestation.