The Nuuk harbor is the largest industrial port in Greenland. It is polluted by a number of contaminants including tributyltin (TBT), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). Here we analyzed melanomacrophage center (MMC) responses in the spleen and kidney of shorthorn sculpins (Myoxocephalus scorpius) from the harbor and three reference sites in Nuuk, West Greenland. The number and area of splenic MMCs in fish from the most polluted station were significantly lower than those from the less polluted stations (p < 0.01). This suggests that the immune response differed between the fish from the contaminated site and those from the reference sites. This indicates that splenic MMCs of shorthorn sculpins could have a biomarker potential for pollutant exposure. This was, however, not the case for renal MMCs. In addition, this study showed that there were effects of body size on the splenic and renal MMC responses. Therefore, in future studies, body size of shorthorn sculpins needs to be considered when investigating splenic and renal MMC responses.