The primary site for pathologic lesions due to M. paratuberculosis infections is the distal part of the small intestine (the ileum and perhaps the jejunum) where the organism enters the animal's tissues after being ingested. The neighboring mesenteric lymph nodes are another site where lesions are common. There is a range of pathology that can be seen in infected deer/elk depending on the stage of infection, the animal's immune system and other factors. Grossly (when the gastrointestinal tract is examined at necropsy), there maybe a complete lack of lesions - the intestine may appear entirely normal. In cases at the other extreme, the intestine appears thickened and corrugated and the neighboring lymph nodes are enlarged and edematous. This thickening and enlargement is due to the influx of inflammatory cells attempting to combat the multiplying organisms in the tissue.		Over the course of the disease, the extent of the tissue damage done by M. paratuberculosis varies. In early phases, no lesions may be detectable. In more advanced stages, lesions are found primarily in the gastrointestinal tract. The ileum may be thickened and corrugated and the neighboring lymph nodes are enlarged. Indications of the infection may be found through microscopic examination of the ileum or lymph nodes even if no signs are visible with the unaided eye. In some cases, the tissue lesions may closely resemble disease caused by other organisms (M. bovis, M. avium).

Caseated and calcified foci have been found in mesenteric lymph nodes of red deer infected with M. paratuberculosis. These lesions were indistinguishable grossly from findings in deer infected with M. avium (Mackintosh, CG; AgResearch Inverna, New Zealand). Carcasses from elk/deer with Johne's disease have been rejected at meat inspection due to the lesions being so similar to those caused by M. bovis. The serosal (outer) surface of the ileum may be tracked by distended lymphatic vessels ("cording"). These animals are often emaciated with a total absence of abdominal fat stores. There are cases with lesions that fall between these two extremes.

When the tissues are examined microscopically, again the animal may present one of a number of pathologic pictures for both clinically and sub-clinically affected deer/elk. The tissues may appear normal in virtually every site. In other cases florid signs of infection such as numerous macrophages and giant cells packed with acid-fast rods may be present. Other cases may fall between these two extremes.