Specific immune priming enables an induced immune response upon repeated pathogen encounter. As a functional analogue to vertebrate immune memory, such adaptive plasticity has been described, for instance, in insects and crustaceans. However, towards the base of the metazoan tree our knowledge about the existence of specific immune priming becomes scattered. Here, we exposed the invasive ctenophore Mnemiopsis leidyi repeatedly to two different bacterial epitopes (Gram-positive or -negative) and measured gene expression. Ctenophores experienced either the same bacterial epitope twice (homologous treatments) or different bacterial epitopes (heterologous treatments). Our results demonstrate that immune gene expression depends on earlier bacterial exposure. We detected significantly different expression upon heterologous compared with homologous bacterial treatment at three immune activator and effector genes. This is the first experimental evidence for specific immune priming in Ctenophora and generally in non-bilaterian animals, hereby adding to our growing notion of plasticity in innate immune systems across all animal phyla.