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During 2008 and 2009, an epidemic affected sponges of the genus Ircinia in the Western Mediterranean. Investigations at a site on the European coast (6°43′08.80′′N; 3°43′52.20′′W) and another on the African coast (35°10′51.00′′N; 2°25′33.00′′W) revealed healthier African populations. The disease started with small pustules on the sponge surface, which subsequently coalesced forming larger, extensive lesions. An ultrastructural study suggested that a twisted rod is the etiological agent. It infected the sponges from the outside, initially killing the cells below the ectosome and then penetrating deeper into the body. The sponges responded to the bacterial progression by secreting concentric barriers of collagen and concentrating phagocytic cells at the diseased zones. This primitive immune system successfully resisted the disease in many instances, although mortality reached 27% in the studied populations. Epidemic outbreaks recur each year in September through November, arguably favored by abnormally high seawater temperatures in August.