This dataset represents collections of Montastraea cavernosa, Porites astreoides, and Pseudodiploria strigosa colonies, no larger than 25 centimeters (cm) × 25 centimeters (cm), from Rupert’s Rock (18°19′39.6ʺN 64°55′33.5ʺW) in St. Thomas, U.S. Virgin Islands. The corals were collected by divers on SCUBA with hammers and chisels (March 2019) and preserved for analysis in April 2019.

Methodology:
Samples were preprocessed by Novogene Co., Ltd. (Davis, CA, USA) for mRNA enrichment using polyA tail capture; the mRNA libraries underwent 150-bp, paired-end sequencing on an Illumina NovaSeq 6000 instrument using the NEBNext Ultra II RNA library prep kit.

Sampling and analytical procedures:
Samples were flash frozen in liquid nitrogen and stored at -80 degrees C until further processing. Total RNA was extracted using the RNAqueous-4PCR total RNA isolation kit (Invitrogen, Life Technologies AM1914). Tissues were lysed using a refrigerated Qiagen TissueLyser II microcentrifuge at 30 oscillations per second for 30 seconds. The elution stage consisted of two consecutive 30-milliliter (mL) elutions. Contaminating DNA and chromatin were removed from the total RNA using the Ambion DNase I (RNase-free) kit (Invitrogen, Life Technologies AM2222).

A combination of reads from stony coral tissue loss disease affected, stony coral tissue loss disease exposed and control (unexposed) holobiont metatranscriptomes (Montastraea cavernosa, Porites astreoides and Pseudodiploria strigosa) were generated from the following samples: Mcav_c3, Mcav_c6, Mcav_c7, Mcav_d2, Mcav_d3, Mcav_d4, Mcav_d6, Mcav_d8, Past_c6, Past_d4, Past_d6 and Pstrig_d5 and given the NCBI accession number: OM030231.

A combination of reads from stony coral tissue loss disease affected, stony coral tissue loss disease exposed and control (unexposed) holobiont metatranscriptomes (Montastraea cavernosa, Porites astreoides and Pseudodiploria strigosa) were generated from the following samples: Mcav_c3, Mcav_c6, Mcav_c7, Mcav_d2, Mcav_d3, Mcav_d4, Mcav_d6, Mcav_d8, Past_c6, Past_d4 and Pstrig_d5 and given the NCBI accession number: OM030232.

Sequence data is available in NCBI Genbank under BioProject accession PRJNA788911 and including NCBI SRA run SRR17230316 - SRR17230326.