Bacterial infections in the lungs of persons with cystic fibrosis are typically composed of multispecies biofilm-like communities, which modulate clinically relevant phenotypes that cannot be explained in the context of a single species culture. Most analyses to-date provide a picture of the transcriptional responses of individual pathogens, however, there is relatively little data describing the transcriptional landscape of clinically-relevant multispecies communities. Harnessing a previously described cystic fibrosis-relevant, polymicrobial community model consisting ofPseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinisandPrevotella melaninogenica, we performed an RNA-Seq analysis to elucidate the transcriptional profiles of the community grown in artificial sputum medium (ASM) as compared to growth in monoculture, without mucin, and in fresh medium supplemented with tobramycin. We provide evidence that, although the transcriptional profile ofP. aeruginosais community agnostic, the transcriptomes ofS. aureusandS. sanguinisare community aware. Furthermore,P. aeruginosaandP. melaninogenicaare transcriptionally sensitive to the presence of mucin in ASM, whereasS. aureusandS. sanguinislargely do not alter their transcriptional profiles in the presence of mucin when grown in a community. OnlyP. aeruginosashows a robust response to tobramycin. Genetic studies of mutants altered in community-specific growth provide complementary data regarding how these microbes adapt to a community context.