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Sponges (phylum Porifera) constantly interact with microbes from the water column while filter-feeding and with the symbiotic partners they harbor within their mesohyl. Despite early observations on differential uptake between symbiont and seawater bacteria, it is still poorly understood how sponges discriminate between different microbial consortia. Initial evidence of the diverse repertoire of sponge immune receptors suggests their involvement in specific microbial recognition, yet experimental data is still scarce. We characterized the transcriptomic response of two sponge species, Aplysina aerophoba and Dysidea avara, upon incubation with two different microbial consortia, which were either enriched from ambient seawater or extracted from A. aerophoba. The sponges were sampled after 1 h, 3 h, and 5 h for RNA-Seq differential gene expression analysis. D. avara showed higher expression levels of genes related to immunity, ubiquitination, and signaling when incubated with A. aerophoba symbionts, than in incubations with seawater microbial consortia. Interestingly, the different bacteria consortia triggered changes in Nucleotide Oligomerization Domain (NOD)-Like Receptors (NLRs) gene expression in D. avara. We here provide the first experimental evidence for NLRs playing a role in distinguishing between different microbes in a sponge. In contrast, the response of A. aerophoba involved comparatively few genes and lacked genes encoding for immune receptors. This indicates that A. aerophoba is less responsive to microbial encounters than D. avara. Our study further reveals different transcriptomic responses between the two sponge …